The Double-Edged Sword Effect of the Fibrinolytic System in Alzheimer's Disease.

IF 7.4 4区医学 Q3 CELL BIOLOGY

Cellular and Molecular Neurobiology Pub Date : 2026-02-27 DOI:10.1007/s10571-026-01699-6

Mingqing Tang, Meimei Liang, Xianying Zhang, Chunzhan Hong, Lichao Ye

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引用次数: 0

Abstract

Alzheimer's disease (AD), the most prevalent neurodegenerative disorder, is fundamentally driven by dysregulation between amyloid-β (Aβ) production and clearance. Although multiple Aβ clearance pathways have been reported, the fibrinolytic system remains the only enzymatically validated degradation route. Notably, a striking paradox is emerging: fibrinolytic agents exhibit both neuroprotective and AD-promoting effects in clinical observations. This duality necessitates urgent investigation into the fibrinolytic system's double-edged sword mechanism in AD pathogenesis. This review provides the first comprehensive analysis of the fibrinolytic system's dichotomous regulatory functions in AD progression, summarizes current advancements in the pathogenesis and therapeutic interventions, and proposes novel research directions. By resolving this molecular paradox, we aim to accelerate transformative breakthroughs in AD prevention and precision medicine strategies. Fibrinolytic System: Neuroprotection vs. Pathogenesis. The fibrinolytic system alleviates AD by directly degrading Aβ and indirectly improving the microenvironment of the central nervous system and cerebrovascular system. Meanwhile, this system also accelerates AD by promoting neuroinflammation and tau hyperphosphorylation.

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纤溶系统在阿尔茨海默病中的双刃剑效应。

阿尔茨海默病（AD）是最常见的神经退行性疾病，从根本上是由淀粉样蛋白-β (Aβ)产生和清除之间的失调所驱动的。尽管已有多种Aβ清除途径的报道，但纤溶系统仍然是唯一经酶学验证的降解途径。值得注意的是，一个惊人的矛盾正在出现：纤维蛋白溶解剂在临床观察中表现出神经保护和ad促进作用。这种双重性迫切需要研究纤溶系统在AD发病中的双刃剑机制。本文首次全面分析了纤溶系统在AD进展中的二元调控功能，总结了目前在AD发病机制和治疗干预方面的研究进展，并提出了新的研究方向。通过解决这一分子悖论，我们的目标是加速阿尔茨海默病预防和精准医学策略的变革性突破。纤溶系统：神经保护与发病机制。纤溶系统通过直接降解Aβ，间接改善中枢神经系统和脑血管系统微环境来缓解AD。同时，该系统还通过促进神经炎症和tau过度磷酸化来加速AD。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cellular and Molecular Neurobiology 生物-神经科学

CiteScore

7.70

自引率

0.00%

发文量

137

审稿时长

4-8 weeks

期刊介绍： Cellular and Molecular Neurobiology publishes original research concerned with the analysis of neuronal and brain function at the cellular and subcellular levels. The journal offers timely, peer-reviewed articles that describe anatomic, genetic, physiologic, pharmacologic, and biochemical approaches to the study of neuronal function and the analysis of elementary mechanisms. Studies are presented on isolated mammalian tissues and intact animals, with investigations aimed at the molecular mechanisms or neuronal responses at the level of single cells. Cellular and Molecular Neurobiology also presents studies of the effects of neurons on other organ systems, such as analysis of the electrical or biochemical response to neurotransmitters or neurohormones on smooth muscle or gland cells.